(S)-alpha-Benzylproline HCl

Background: In women undergoing cesarean delivery under spinal anesthesia with intrathecal morphine, transversus abdominis plane (TAP) block with bupivacaine hydrochloride (HCl) may not improve postsurgical analgesia. This lack of benefit could be related to the short duration of action of bupivacaine HCl. A retrospective study reported that TAP block with long-acting liposomal bupivacaine (LB) reduced opioid consumption and improved analgesia following cesarean delivery. Therefore, we performed a prospective multicenter, randomized, double-blind trial examining efficacy and safety of TAP block with LB plus bupivacaine HCl versus bupivacaine HCl alone. Methods: Women (n = 186) with term pregnancies undergoing elective cesarean delivery under spinal anesthesia were randomized (1:1) to TAP block with LB 266 mg plus bupivacaine HCl 50 mg or bupivacaine HCl 50 mg alone. Efficacy was evaluated in a protocol-compliant analysis (PCA) set that was defined a priori. The primary end point was total postsurgical opioid consumption (oral morphine equivalent dosing [MED]) through 72 hours. Pain intensity was measured using a visual analog scale. Adverse events (AEs) after treatment were recorded through day 14. Results: Total opioid consumption through 72 hours was reduced with LB plus bupivacaine HCl versus bupivacaine HCl alone (least squares mean [LSM] [standard error (SE)] MED, 15.5 mg [6.67 mg] vs 32.0 mg [6.25 mg]). This corresponded to an LSM treatment difference of -16.5 mg (95% confidence interval [CI], -30.8 to -2.2 mg; P = .012). The area under the curve of imputed pain intensity scores through 72 hours supported noninferiority of LB plus bupivacaine HCl versus bupivacaine HCl alone (LSM [SE], 147.9 [21.13] vs 178.5 [19.78]; LSM treatment difference, -30.6; 95% CI, -75.9 to 14.7), with a prespecified noninferiority margin of 36 (P = .002). In an analysis of all treated patients, including those not meeting criteria for inclusion in the PCA, there was no difference in postsurgical opioid consumption between groups. In the LB plus bupivacaine HCl group, 63.6% of patients experienced an AE after treatment versus 56.2% in the bupivacaine HCl-alone group. Serious AEs after treatment were rare (≈3% in both groups). Conclusions: TAP block using LB plus bupivacaine HCl as part of a multimodal analgesia protocol incorporating intrathecal morphine resulted in reduced opioid consumption after cesarean delivery in the PCA set. Results suggest that with correct TAP block placement and adherence to a multimodal postsurgical analgesic regimen, there is an opioid-reducing benefit of adding LB to bupivacaine TAP blocks after cesarean delivery (ClinicalTrials.gov identifier: NCT03176459).

The title complex salt, (C12H16NO2)[PdCl2(C12H14NO2)], is of inter-est with respect to organic and organometallic catalysis. The compound crystallizes as very small orange-red irregular prisms and the asymmetric unit contains three crystallographically distinct cation-anion pairs. The coordination geometry about the palladium atoms is square-planar with the chloride ligands cis to one another. The structure displays N-H⋯Cl and O-H⋯O hydrogen bonding such that the N-H⋯Cl hydrogen bonds align the cation-anion pairs in a linear fashion along [001], with the O-H⋯O hydrogen bonds connecting these linear strands along [100] and [010].

In the centrosymmetric title compound, [Co(4)Cl(4)(C(3)H(6)S)](4)], the two independent Co(III) ions are each coordinated in a distorted tetra-hedral geometry by one C, one Cl and two S atoms. The mol-ecules are stabilized by C-H⋯Cl hydrogen bonds. In the crystal, inter-molecular C-H⋯Cl and C-H⋯S hydrogen bonds with R(2) (2)(8), R(4) (2)(8) and R(2) (2)(6) ring motifs generate a polymeric network.